The technology to extract objective, quantitative information from in vivo magnetic resonance (MR) images has not kept pace with the improved spatial and contrast resolution of MR images. With recent advances in image processing, however, it is now possible to exploit more fully information contained in MR images. The purpose of the present proposal is to apply newly developed MR image processing techniques to high spatial resolution MR images in order to quantify in vivo differences between the brains of normal control subjects and patients afflicted with schizophrenia. The application of these techniques to the investigation of schizophrenia is promising because brain anomalies are often subtle and may not be present in all patients. We have begun to apply these techniques and have some exciting and promising, albeit preliminary findings from a small sample in which schizophrenics, compared to normals, showed: 1) left lateralized volume reductions in anterior hippocampus, parahippocampal gyrus (also on the right), and neocortical superior temporal gyrus (STG); 2) a high correlation between left posterior STG volume and amount of thought disorder (r=0.81); 3) a non-statistically significant but interesting increase in white matter in anterior cingulate gyrus that might be consistent with an increase in vertical axons reported by Benes in a post-mortem study of schizophrenics; and 4) a more disorganized, non-parallel gyral pattern in the temporal lobe. These findings are, however, preliminary and the inclusion of a larger sample is essential to increase the statistical power. We now propose to broaden our studies and to apply computerized image processing techniques to MR scans obtained from 75 male, right-handed, ch ronic schizophrenics (15 per year) and 75 age- sex- and parental social class- matched normal controls.